title: Insulin degludec once-daily in type 2 diabetes: simple or step-wise titration (BEGIN: once simple use).
abstract: BACKGROUND
  Insulin degludec (IDeg) is a new basal insulin in development with a flat, ultra-long action profile that may permit dosing using a simplified titration algorithm with less frequent self-measured blood glucose (SMBG) measurements and more simplified titration steps than currently available basal insulins.
  
  
  METHODS
  This 26-week, multi-center, open-label, randomized, treat-to-target study compared the efficacy and safety of IDeg administered once-daily in combination with metformin in insulin-naïve subjects with type 2 diabetes using two different patient-driven titration algorithms: a "Simple" algorithm, with dose adjustments based on one pre-breakfast SMBG measurement (n = 111) versus a "Step-wise" algorithm, with adjustments based on three consecutive pre-breakfast SMBG values (n = 111). IDeg was administered using the FlexTouch® insulin pen (Novo Nordisk A/S, Bagsværd, Denmark), with once-weekly dose titration in both groups.
  
  
  RESULTS
  Glycosylated hemoglobin (HbA1c) decreased from baseline to week 26 in both groups (-1.09%, IDegSimple; -0.93%, IDegStep-wise). IDegSimple was non-inferior to IDegStep-wise in lowering HbA1c [estimated treatment difference (IDegSimple - IDegStep-wise): -0.16% points (-0.39; 0.07)95% CI]. Fasting plasma glucose was reduced (-3.27 mmol/L, IDegSimple; -2.68 mmol/L, IDegStep-wise) with no significant difference between groups. Rates of confirmed hypoglycemia [1.60, IDegSimple; 1.17, IDegStep-wise events/patient year of exposure (PYE)] and nocturnal confirmed hypoglycemia (0.21, IDegSimple; 0.10, IDegStep-wise events/PYE) were low, with no significant differences between groups. Daily insulin dose after 26 weeks was 0.61 U/kg (IDegSimple) and 0.50 U/kg (IDegStep-wise). No significant difference in weight change was seen between groups by week 26 (+1.6 kg, IDegSimple; +1.1 kg, IDegStep-wise), and there were no clinically relevant differences in adverse event profiles.
  
  
  CONCLUSIONS
  IDeg was effective and well tolerated using either the Simple or Step-wise titration algorithm. While selection of an algorithm must be based on individual patient characteristics and goals, the ability to attain good glycemic control using a simplified titration algorithm may enable patient empowerment through self-titration, improved convenience, and reduced costs.
authors.affiliation: Scripps Whittier Diabetes Institute, 9894 Genesee Ave, La Jolla, CA 92037, USA. Tsimikas.Athena@scrippshealth.org
authors.forename: Athena
authors.initials: A
authors.lastname: Philis-Tsimikas
authors.forename: Meryl
authors.initials: M
authors.lastname: Brod
authors.forename: Marcus
authors.initials: M
authors.lastname: Niemeyer
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Ocampo Francisco
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Rothman
mesh_terms: D000368:Aged; D000465:Algorithms; D015190:Blood Glucose Self-Monitoring; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D049528:Insulin, Long-Acting / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; C571886:insulin degludec; D008687:Metformin